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A Proof of Concept Study for 6 Month Treatment in Patients With C3 Glomerulopathy (C3G)

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ClinicalTrials.gov Identifier: NCT03369236
Recruitment Status : Recruiting
First Posted : December 11, 2017
Last Update Posted : June 29, 2018
Sponsor:
Information provided by (Responsible Party):
Achillion Pharmaceuticals

Brief Summary:
The primary purpose of this proof of concept clinical study is to evaluate the efficacy and safety of the study drug, ACH-0144471, in participants who have been diagnosed with either C3GN or dense deposit disease (DDD) based on renal biopsy. Participants will be randomized 1:1 to receive either study drug ACH-0144471 or placebo for a period of 6 months.

Condition or disease Intervention/treatment Phase
C3 Glomerulopathy C3 Glomerulonephritis Dense Deposit Disease Drug: ACH-0144471 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, Double-Blind
Masking: Double (Participant, Investigator)
Masking Description: Investigator and subject blinded; Sponsor Open
Primary Purpose: Treatment
Official Title: A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-Controlled Study of ACH-0144471 Treatment for 6 Months in Patients With C3 Glomerulopathy (C3G)
Actual Study Start Date : June 12, 2018
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : October 2019


Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo tablets 3 times daily (TID) for the first 2 weeks (Dose Adjustment Period) with the opportunity for dose adjustment, then continued for an additional 6 months (Treatment Period). At the time of treatment completion, drug will be tapered as appropriate.
Drug: Placebo
All participants randomized to the placebo arm will receive 6 months of placebo medication. At the time of treatment completion, drug will be tapered as appropriate.

Experimental: ACH-0144471
ACH-0144471 tablets at a starting dose of 100 mg TID for the first 2 weeks (Dose Adjustment Period) with the opportunity for dose adjustment, then continued for an additional 6 months (Treatment Period). At the time of treatment completion, drug will be tapered as appropriate.
Drug: ACH-0144471
All participants randomized to the treatment arm will receive 6 months of active study medication ACH-0144471. At the time of treatment completion, drug will be tapered as appropriate.
Other Names:
  • ACH-4471
  • ACH4471
  • 4471




Primary Outcome Measures :
  1. Change from baseline in renal biopsy, based on a score incorporating changes in both the activity index and C3 staining, at the end of 6 months of treatment [ Time Frame: Baseline, 6 months ]
  2. Number of participants with significant improvement relative to baseline in proteinuria at the end of 6 months of treatment [ Time Frame: 6 months ]
  3. Percent of participants with significant improvement relative to baseline in proteinuria at the end of 6 months of treatment [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. Change from baseline in proteinuria over the 6 months of treatment for participants meeting proteinuria inclusion criterion at entry of the study [ Time Frame: Baseline, 6 months ]
  2. Percent change from baseline in proteinuria over the 6 months of treatment for participants meeting proteinuria inclusion criterion at entry of the study [ Time Frame: Baseline, 6 months ]
  3. Change from baseline in eGFR over the 6 months of treatment for participants with an abnormal eGFR at entry of the study [ Time Frame: Baseline, 6 months ]
  4. Percent change from baseline in eGFR over the 6 months of treatment for participants with an abnormal eGFR at entry of the study [ Time Frame: Baseline, 6 months ]
  5. Number of participants with significant improvement relative to baseline in eGFR at the end of 6 months of treatment, for those with an abnormal eGFR at study entry [ Time Frame: 6 months ]
  6. Percent of participants with significant improvement relative to baseline in eGFR at the end of 6 months of treatment, for those with an abnormal eGFR at study entry [ Time Frame: 6 months ]
  7. Number of participants with serious adverse events (SAEs), Grade 3 and above adverse events (AEs), Grade 3 and above laboratory abnormalities, and events leading to discontinuation of study drug. [ Time Frame: 6 months ]
  8. Percent of participants with serious adverse events (SAEs), Grade 3 and above adverse events (AEs), Grade 3 and above laboratory abnormalities, and events leading to discontinuation of study drug. [ Time Frame: 6 months ]


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Ages Eligible for Study:   17 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Initial diagnosis of C3GN or DDD 3 months prior to the first dose of study drug and prior to age 55 years.
  • Confirmation of DDD or C3 glomerulonephritis (C3GN) diagnosis by review of a renal biopsy obtained no more than 30 days (and preferably within 2 weeks) of first dose of study drug by the study's central pathology laboratory
  • Clinical evidence of ongoing disease based on significant proteinuria, defined as ≥1 g/day of protein in a 24-hour urine, attributable to C3G disease in the opinion of the Principal Investigator (PI), and present prior to study entry and confirmed during Screening
  • Must be willing to comply with study-specific vaccination requirements, including those for N. meningitidis, H. influenzae, and S. pneumonia

Exclusion Criteria:

  • Have a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study
  • Have ever received ACH-0144471
  • Have more than 50% fibrosis or more than 50% of glomeruli with cellular crescents on the pre-treatment renal biopsy
  • Have an estimated GFR <30 mL/min for participants19 years of age and older (based on CKD-EPI creatinine equation [2009]), and <30 mL/min/1.73 m2 for participants <19 years old (based on "Bedside Schwartz" equation [2009]) at the time of screening or at any time over the preceding four weeks
  • Have C4 levels <80% lower limit of normal (LLN)
  • Is a renal transplant recipient or receiving renal replacement therapy
  • Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant
  • Have evidence of monoclonal gammopathy of unclear significance (MGUS), infections, malignancy, autoimmune diseases, or other conditions to which C3G may be secondary
  • Have other renal diseases that would interfere with interpretation of the study
  • Have comorbid conditions that would interfere with completion of the trial (e.g., malignancies, congestive heart failure, recent myocardial infarction)
  • Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
  • Have a history of febrile illness, a body temperature >38°C, or other evidence of a clinically significant active infection, within 14 days prior to study drug administration
  • Have evidence of human immunodeficiency virus (HIV) (positive serology for HIV antibody [HIV Ab]), hepatitis B infection (positive hepatitis B surface antigen [HbsAg]), or hepatitis C infection (positive anti-HCV antibody [HCV Ab]) at Screening or historically
  • Have any of the following laboratory abnormalities at screening:

    • Alanine transaminase (ALT) > upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) > ULN
    • Absolute neutrophil counts (ANC) <1,000/μL
    • Total bilirubin >1.5× ULN
    • Indirect bilirubin > ULN
    • Any laboratory abnormality that, in the opinion of the PI, would make the participant inappropriate for the study

NOTE: Additional inclusion/exclusion criteria will apply, per protocol


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03369236


Contacts
Contact: Clinical Operations 203-752-5566 C3GTrialInquiries@achillion.com

Locations
United States, Colorado
Children's Hospital of Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Bradley Dixon         
Principal Investigator: Bradley Dixon         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Carla Nester         
Principal Investigator: Carla Nester         
United States, Maryland
John Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: John Sperati         
Principal Investigator: John Sperati         
United States, Minnesota
Mayo Clinic Rochester Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Fernando Fervenza         
Principal Investigator: Fernando Fervenza         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Gerald Appel         
Principal Investigator: Gerald Appel         
New York University School of Medicine Not yet recruiting
Queens, New York, United States, 11040
Contact: Howard Trachtman         
Principal Investigator: Howard Trachtman         
United States, Texas
Baylor Clinic Not yet recruiting
Houston, Texas, United States, 77030
United Kingdom
Imperial College of London Not yet recruiting
London, United Kingdom
Contact: Mathew Pickering         
Principal Investigator: Matthew Pickering         
Sponsors and Collaborators
Achillion Pharmaceuticals

Responsible Party: Achillion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03369236     History of Changes
Other Study ID Numbers: ACH471-204
2017-000663-33 ( EudraCT Number )
First Posted: December 11, 2017    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Achillion Pharmaceuticals:
factor D
fD
alternative pathway
complement mediated disease
Membranoproliferative Glomerulonephritis
Primary MPGN
MPGN
Mesangiocapillary Glomerulonephritis
idiopathic MPGN
DDD
C3GN

Additional relevant MeSH terms:
Glomerulonephritis
Glomerulonephritis, Membranoproliferative
Nephritis
Kidney Diseases
Urologic Diseases
Immune System Diseases